The major objective of our studies is to characterize cell surface structures on T and B lymphocytes as well as on non-T accessory cells (AC) which, in addition to the specific antigen receptor, are involved in the process of lymphocyte activation. Over the past 4 years we have developed a number of monoclonal antibodies (Mabs) to mouse T lymphocyte cell surface antigens which are capable of stimulating or inhibiting T cell triggering. One group of these reagents is directed to the receptor for interleukin-2 (IL-2) on activated murine lymphocytes. These Mabs have been used to further characterize the role of non-T AC in the induction of IL-2 receptor expression and to isolate and sequence a cDNA that contains the entire coding region of the murine IL-2 receptor. A new lymphokine, IL-2 inhibitor, which is capable of neutralizing the biologic activity of Il-2 has been characterized and purified to apparent homogeneity. Newly developed Mabs to the Thy-1 antigen were used to demonstrate the critical role of this molecule in signal transduction following transfection of the Thy-1 gene into human cells. Lastly, we have shown that the L3T4 antigen, a marker for a subpopulation of T cells, may play a dual role in T cell function by interacting with target molecules on AC and by subsequently functioning as a signal transmitter to other cell surface molecules on the T cell. The ultimate goals of our studies are to fully understand the regulatory mechanisms that control T cell activation and differentiation. Mabs to lymphocyte surface antigens should prove to be useful tools in these studies and may also prove to be attractive candidates for in vivo therapeutic use in attempts to modulate or abrogate an ongoing immune response.